Microfluidic system and methods of use

• US 6,632,619 B1
• Filed: 05/16/1997
• Issued: 10/14/2003
• Est. Priority Date: 05/16/1997
• Status: Expired due to Fees

• Current Assignee: Alberta Research Council, Zellchip Technologies Inc.
• Original Assignee: The Governors of the University of Alberta (University of Alberta)
• Inventors: Andersson, Per, Smith, Richard, Szarka, Roderick, Li, Paul C. H., Harrison, Daniel Jed
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US08/858,087
• Time in Patent Office: 2,342 Days
• Field of Search: 435/7.24, 435/7.2, 435/287.1, 73/614, 250/341, 356/39, 422/55-58, 436/500, 436/514, 436/518, 436/805
• US Class Current: 435/7.2
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B81B 1/00 Devices without movable or flexible elements, e.g. microcapillary devices
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

This invention relates to a novel microfluidic device and methods of using this device to conduct in vitro studies on the reaction and effects of various compounds on cells. More particularly, it relates to a method for using stop flow in a microfluidic system to study the effect of compounds on individual cells.

Claims

1. A method of observing the effect of one or more candidate compounds on cells in a microfluidic device comprising:

(a) providing a microfluidic device comprising a main flow path comprising an outlet, at least two inlet flow paths and a detection zone, wherein at least one inlet flow path intersects and merges with the main flow path at the detection zone, wherein the intersection of inlet flow paths with the main flow path is at an upstream angle of less than 90°

;

(b) applying into the microfluidic device at least one cell which flows into a first inlet flow path and a candidate compound to a second inlet flow path;

(c) inducing flow of the cells and the candidate compound toward the outlet;

(d) allowing the at least one cell to mix with the candidate compound in the detection zone; and

(e) observing the effect of the candidate compound on the cells in the detection zone.

2. The method of claim 1 wherein the candidate compound being studied is an inhibitor, and the cells are lymphocytes.

3. The method of claim 1 wherein the flow paths are coated with a substance selected from the group consisting of proteins, glycoproteins, phospholipids, hydrophilic polymers and hydrophobic polymers.

4. The method of claim 2 wherein the flow paths are coated with protein.

5. The method of claim 3 wherein the flow is induced by an electric force.

6. The method of claim 4 wherein the flow is induced by positive or negative fluid pressure.

7. The method of claim 1, wherein the intersection of inlet flow paths with the main flow path is at an upstream angle of less than 70°

.

8. The method of claim 1, wherein the intersection of inlet flow paths with the main flow path is at an upstream angle of less than 50°

.